5,8-二取代1-四氢萘酮曼尼希碱的镇痛与镇静活性

Analgesic and tranquilizing activity of 5,8-disubstituted 1-tetralone Mannich bases.

作者信息

Welch W M, Harbert C A, Sarges R, Stratten W P, Weissman A

出版信息

J Med Chem. 1977 May;20(5):699-705. doi: 10.1021/jm00215a016.

Abstract

5,8-Disubstituted 1-tetralone Mannich bases represent semirigid variants of classical (i.e., chlorpromazine) neuroleptic agents. 8-Chloro-5-methoxy-2-morpholinomethyl-1-tetralone exhibits neuroleptic potency in the thiothixene range in animal models. Of greater potential interest, however, is the analgesic potency of the 8-chloro-5-methoxy-2-pyrrolidinomethyl analogue which was in the morphine range. This compound did not induce tolerance nor was its activity reversed by naloxone. Structure-activity relationships of the series are discussed.

摘要

5,8-二取代的1-四氢萘酮曼尼希碱代表经典（即氯丙嗪）抗精神病药物的半刚性变体。8-氯-5-甲氧基-2-吗啉甲基-1-四氢萘酮在动物模型中表现出硫利达嗪范围内的抗精神病效力。然而，更具潜在意义的是8-氯-5-甲氧基-2-吡咯烷甲基类似物的镇痛效力，其效力处于吗啡范围内。该化合物不会诱导耐受性，其活性也不会被纳洛酮逆转。讨论了该系列的构效关系。